Archive for the 'Immune-based Therapies' Category
December 31st, 2010. Expression and regulation of B7-H3 immunoregulatory receptor, in human mesothelial and mesothelioma cells: immunotherapeutic implications
In vivo, while B7-H3 was expressed in all 13 tumor biopsies of the epithelial variant, with high levels in 54% of cases, it was rarely detectable in spindle type MM in which 1/5 biopsies weakly expressed B7-H3. These findings suggest that B7-H3 is a promising target for new immunotherapeutic strategies in MM, with particular emphasis in the epithelial variant.
December 17th, 2008. Systemic blockade of transforming growth factor-beta signaling augments the efficacy of immunogene therapy
E7 vaccination therapy. The addition of TGF-beta blocking agents in clinical trials of immunotherapies may increase efficacy.
December 12th, 2008. Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy
Indeed, we observed that the drug gemcitabine, which does not deplete cycling regulatory T cells, eradicates established tumors in mice only when CD25+ CD4+ T cells are concurrently depleted. Cyclophosphamide could be used to achieve regulatory T cell depletion in combination with chemotherapy.
November 21st, 2008. Secretion of N-ERC/mesothelin and expression of C-ERC/mesothelin in human pancreatic ductal carcinoma
Although C-ERC/mesothelin was frequently expressed in human pancreatic ductal carcinoma, serum N-ERC/mesothelin concentration of cancer patients was equivalent to healthy controls. N-ERC/mesothelin was not useful as a serum marker of pancreatic ductal carcinoma, but because of frequent expression, C-ERC/mesothelin might be useful as a target of molecular imaging and immunotherapy.
October 4th, 2008. Expression of the embryonic lethal abnormal vision-like protein HuR in human mesothelioma
Conclusions: The current results suggested that HuR plays a role in tumor progression in mesothelioma and that COX-2 may be a target of its activity in neoplastic cells. Together, these observations indicate that strategies aiming toward the modulation of HuR may have a potential clinical benefit in mesothelioma.
August 30th, 2008. Lysophosphatidic acid stimulates the proliferation and motility of malignant pleural mesothelioma cells through lysophosphatidic acid receptors, LPA1 and LPA2
These results indicate that LPA is a critical factor on proliferation though LPA1, and on motility though LPA2 in MPM cells. Therefore, LPA and LPA receptors, LPA2 as well as LPA1, represent potential therapeutic targets for patients with MPM.
August 14th, 2008. Enhanced antitumor therapy by inhibition of p21waf1 in human malignant mesothelioma
Conclusions: These results indicated that p21 might play an important role in chemosensitivity to anticancer agents, and the suppression of its expression might be a potential therapeutic target for MPM.
June 24th, 2008. Phosphorylation and localization of protein-zero related (PZR) in cultured endothelial cells
To see if tyrosine kinases other than Src are also capable of phosphorylating PZR, the authors cotransfected HEK293 cells with PZR and one of several tyrosine kinases and found that c-Src, c-Fyn, c-Lyn, Csk, and c-Abl, but not c-Fes, phosphorylated PZR and increased PZR/SHP-2 interaction. These results suggest that PZR is a cell adhesion protein that may be involved in SHP-2-dependent signaling at interendothelial cell contacts.
June 4th, 2008. Malignant mesothelioma 2008
Novel therapies including intrapleural chemotherapy, photodynamic therapy and hyperthermic perfusion have also been used with some success. Finally there are several attempts at immunomodulating and targeted treatments, which are in phase I/II trials.
Posted in Causation, Chemotherapy, Determining Efficacy, Diagnosis & Differentiation, Full Archive, General, Immune-based Therapies, New & Novel, Occupational Asbestos Exposure, Photodynamic Therapy (PDT), Radiation, Serum Marker/Blood Test, Survival, SV40, Treatment, Type of Assessment: | No Comments »
May 21st, 2008. Human Tumor-Derived Exosomes Down-Modulate NKG2D Expression
This hyporesponsiveness was evident even in the presence of IL-15, a strong inducer of NKG2D. Our data show that NKG2D is a likely physiological target for exosome-mediated immune evasion in cancer.
April 22nd, 2008. Increased exosome production from tumour cell cultures using the Integra CELLine Culture System
This simple culture system is a cost effective, useful method for significantly increasing the quantity of exosomes available from cultured cells, without detrimental effects. This tool should prove advantageous in future studies of exosome-immune modulation in cancer and other settings.
April 1st, 2008. Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma
Conclusion: The presence of high levels of CD8+ tumor-infiltrating lymphocytes is associated with better prognosis in patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma. The stimulation of CD8+ lymphocytes can be a potential therapeutic strategy to improve outcome.
Posted in Diagnosis & Differentiation, Extrapleural Pneumonectomy (EPP), Full Archive, Immune-based Therapies, Immunohistochemistry or IHC, Pleural, Surgery, Survival, Treatment, Type of Assessment:, Type of Mesothelioma: | No Comments »
March 6th, 2008. Targeted drug delivery to mesothelioma cells using functionally selected internalizing human single-chain antibodies
We have further exploited the internalizing function of these scFvs to achieve targeted intracellular drug delivery to mesothelioma cells. We showed that scFv-targeted immunoliposomes were efficiently and specifically taken up by both epithelioid and sarcomatous mesothelioma cells, but not control cells, and immunoliposomes encapsulating the small-molecule drug topotecan caused targeted killing of both types of mesothelioma cells in vitro.
January 23rd, 2008. Targeting the Effector Site with IFN-{alpha}{beta}-Inducing TLR Ligands Reactivates Tumor-Resident CD8 T Cell Responses to Eradicate Established Solid Tumors
Instead, the antitumor response was critically dependent on the reactivation of tumor-resident CD8 T cell responses. These studies suggest that, once reactivated, pre-existing local CD8 T cell responses are sufficient to resolve established tumors and that in situ type I IFN is a determining factor.
December 21st, 2007. Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin
The preclinical data obtained from our studies warrants pursuing clinical testing of MORAb-009. We have in fact initiated a Phase I clinical study enrolling patients with mesothelin-positive pancreatic, mesothelioma, non-small cell lung and ovarian cancers.
December 7th, 2007. CD200: A putative therapeutic target in cancer
Moreover, we show that CD200 expression is associated with tumor progression in various cancers. Taken together, these data suggest that CD200 is a potential therapeutic target and prognostic factor for a large array of malignancies.
November 28th, 2007. Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: Therapeutic targets
Stem cell therapy and gene replacement offer the prospect of novel approaches that are likely in the near future to play a definitive role in the treatment of advanced lung cancer. Furthermore, with their apparent minimal toxicity to normal tissues, the newer molecular targets represent attractive investigational directions for innovative cancer therapies.
November 3rd, 2007. Flowcytometric immunophenotyping of peripheral-blood leukocytes in relation to immunopathology and cellular proliferation of pleural mesothelioma
In conclusion, mesothelioma might be associated with modulation of the tumoricidal effect of cytotoxic T lymphocytes in relation to tumor differentiation and its proliferative potentiality. Immunophenotyping analysis of leukocytes may reflect the competence of immune system against malignancy and act as an additive prognostic parameter for mesothelioma progression and probably expecting response to oncotherapy protocols.
October 20th, 2007. Mesothelin targeted cancer immunotherapy
These include SS1P (CAT-5001) a recombinant immunotoxin targeting mesothelin, MORAb-009 a chimeric anti-mesothelin monoclonal antibody and CRS-207 a live-attenuated Listeria monocytogenes vector encoding human mesothelin. These ongoing clinical trials will help define the utility of mesothelin as a target for cancer therapy.
October 9th, 2007. Alpha-Tocopheryl succinate: Toxicity and lack of anti-tumour activity in immuno-competent mice
Toxicity of α-TOS has not been reported to date perhaps due to a lack of studies conducted in fully immuno-competent hosts. Our results suggest that the translation of animal studies to clinical treatment with α-TOS requires careful consideration.
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